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Abstract BACKGROUND: A history of prolonged and excessive consumption of alcohol increases the risk for infections. The goal of this study was to investigate circulating white blood cells (WBC) differentiated by flow cytometry and neutrophil CD64 expression in excessive alcohol drinkers versus abstinent or moderate drinkers, and in those with or without infection, in medical patients admitted to the intensive care unit (ICU). METHODS: All patients admitted between September 2009 and March 2010 with an ICU-stay of 3 days or more were eligible for inclusion. Upon admission, hematological exams were conducted by flow cytometry. RESULTS: Overall, 281 adult were included, with 37\% identified as at-risk drinkers. The only significant difference found in circulating WBC between at-risk and not-at-risk drinkers was a lower number of B lymphocytes in at-risk drinkers (P = 0.002). Four groups of patients were defined: not-at-risk drinkers with no infection (n = 66); not-at-risk drinkers with infection (n = 112); at-risk drinkers with no infection (n = 53); and at-risk drinkers with infection (n = 50). Whilst the presence of infection significantly reduced levels of noncytotoxic and cytotoxic T lymphocytes and significantly increased levels of CD16- monocytes in not-at-risk drinkers, with variation related to infection severity, infection had no effect on any of the variables assessed in at-risk drinkers. Post-hoc comparisons showed that B-lymphocyte, noncytotoxic, and cytotoxic T lymphocyte and CD16- counts in at-risk drinkers were similar to those in not-at-risk drinkers with infection and significantly lower than those in not-at-risk drinkers without infection. Neutrophil CD64 index varied significantly between groups, with variations related to infection, not previous alcohol consumption. CONCLUSIONS: These results show that chronic alcohol exposure has an impact on the immune response to infection in critically ill medical patients. The absence of significant variations in circulating WBC seen in at-risk drinkers according to the severity of infection is suggestive of altered immune response.